Inhibitory effect of dihydromyricetin on the proliferation of JAR cells and its mechanism of action

Dihydromyricetin (DMY) is a novel natural drug with antitumor activity against some cancer cells without obvious toxicity. Previously, its apoptotic effect on human choriocarcinoma was detected. The present study further investigated the therapeutic potential of DMY as a new drug for the treatment of choriocarcinoma, as well as its anti-proliferative effect and mechanism of action. The short-term proliferation of JAR cells was determined by MTT assay, whereas the effect of DMY on long-term cell proliferation was determined by colony forming assay. Flow cytometry was used to detect changes in the cell cycle. Furthermore, western blotting was used to detect the expression levels of proliferation-associated proteins such as cyclin A1, cyclin D1, SMAD3 and SMAD4. Reverse transcription-quantitative PCR (RT-qPCR) was used to quantify mRNA expression levels. The results indicated that DMY inhibited short and long-term proliferation of JAR cells in a concentration-dependent manner. Flow cytometry demonstrated S/G(2)/M cell cycle arrest, and western blotting revealed the downregulation of SMAD3, SMAD4, cyclin A1 and cyclin D1 expression levels. The results of RT-qPCR and western blotting were consistent. Overall, the findings of the present study suggest that DMY inhibits the proliferation of human choriocarcinoma JAR cells, potentially through cell cycle arrest via the downregulation of cyclin A1, cyclin D1, SMAD3 and SMAD4 expression levels.